JNCI Podcast: Issue 23 Transcript

Hi and welcome to the JNCI podcast. I’m Steve Graff, JNCI’s assistant news and media editor, and I’ll be taking you through the next issue of the Journal of the National Cancer Insitute.

Up first: Does the news media exaggerate fears and hopes in coverage of cancer research? A new editorial tackles this question, as well as provides guidance for both the media and journals to help alleviate the problem. Also in this issue, there are studies that looked the age-specific evaluation of HPV DNA testing vs cytology screening, the adverse symptom reporting by patients vs clinicians. and erythropoiesis-stimulating agents and their association with venous thromboembolism. Also in this issue, a study looked at detecting overall survival Benefit derived from progression free-survival. And in this issue’s brief communication, researchers looked at the effects of aspirin and folic Acid on inflammation markers for colorectal adenomas.

All that in more detail coming up next…

An editorial published online November 20 discusses the exaggerated fears and hopes that often appear in news coverage of cancer research.

Lisa M. Schwartz, and Steven Woloshin, of Center for Medicine and the Media at the Dartmouth Institute for Health Policy and Clinical Practice in New Hampshire, and Barnett S. Kramer, editor-in-chief of the JNCI, use recent media coverage of two studies from the New England Journal of Medicine and the JNCI to demonstrate their point.

Coverage of trial results of the new anti-cancer drug olaparib, which appeared in the NEJM, exaggerated hope in many ways. One national news outlet claimed the drug “was the most important cancer breakthrough of the decade,” but failed to note that the study was uncontrolled (so there is no way to know if the drug accounted for the findings), and very preliminary (it is not known if the findings will ever translate into longer life).

The editorialists also point to coverage of a JNCI article on alcohol consumption and cancer risk among women, which may have caused unwarranted fear: “A drink a day raises women’s risk of cancer,” read one newspaper headline. Unfortunately, the coverage did not provide the magnitude of the risk. Comparing the highest level of drinking (≥15 drinks a week) to the lowest (one to two drinks per week), the investigators observed a 0.6% absolute increase in the risk of breast cancer diagnosis: from 2% to 2.6% for more than 7 years.

Journalists are not the only ones to blame, though, according to the editorialists. Medical journals sometimes leave important elements out of studies. In many cases, absolute risks and study limitations are omitted from the abstracts and journal press releases.

HPV DNA testing with cytology triage is more sensitive than conventional cytology screening for detecting cervical lesions, according to a new study published online November 9.

HPV DNA testing has shown higher sensitivity than conventional cytology screening for detecting cervical lesions, but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened.

Maarit Leinonen, of the Mass Screening Registry, Finnish Cancer Registry in Helsinki, and colleagues compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening. Finnish women aged 25–65 years were sent randomized invitations for HPV DNA testing with cytology triage or conventional screening.

Overall, primary HPV DNA screening with cytology triage was more sensitive than conventional screening for detecting cervical lesions. Among women younger than 35 years, those who got HPV DNA screening were referred for colposcopy more often than those who got conventional screening. Among women aged 35 years or older, HPV DNA testing with cytology triage was more sensitive and more specific than conventional screening, had a higher precision rate, and was associated with fewer colposcopy referrals and follow-up tests.

In an accompanying editorial, Eduardo L. Franco, said that “this finding underscores the importance of cytology as a triage test in preserving the specificity of the HPV DNA screening approach.”

A study published online November 17 found that clinician’s and patient’s adverse symptom reports may be discrepant from each other, but provide complementary, clinically meaningful information

In cancer clinical trials, it is currently standard for clinicians rather than patients to report adverse symptoms such as nausea or fatigue. Patient self-reporting is an alternative approach that is not well studied and is of unknown scientific value.

Ethan Basch, M.D., of the Health Outcomes Group, Memorial Sloan-Kettering Cancer Center in New York, and colleagues gathered data from more than 160 lung cancer patients and their clinicians for six common symptoms reported via the standard adverse event reporting lexicon in oncology trials, the National Cancer institute’s Common Terminology Criteria for Adverse Events.

Patients generally reported adverse symptoms earlier, more frequently, and with greater severity than their clinicians. Patient-reported symptoms were more highly associated with day-to-day health status, whereas clinician reports were more predictive of death and hospitalization.

In an accompanying editorial, Carolyn Gotay., of the School of Population and Public Health, University of British Columbia, in Vancouver, commends the study’s collection of comparable data from both groups and impressive response rates, but points out some of the potential biases in reports that arise from the patient’s perspective: motivation, interpretation, expectations, and personality.

Use of erythropoiesis-stimulating agents, or ESAs, is associated with an increased risk of venous thromboembolism, according to study published online November 10.

ESAs stimulate red blood cell production and therefore were approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism (the disease that includes deep vein thrombosis and pulmonary embolism) and mortality exist.

Dawn L. Hershman, of Columbia University Medical Center in New York, and colleagues analyzed the association between agent use and venous thromboembolism and overall survival in patients who were 65 years or older and diagnosed with colon, non-small cell lung, or breast cancer or diffuse large B-cell lymphoma in 1991-2002. Patients were identified in the Surveillance, Epidemiology, and End Results–Medicare database.

More patients who received an ESA than patients who did not developed venous thromboembolism. Overall survival was similar in both groups. The number of patients receiving ESAs increased approximately 10-fold from 1991 through 2002. The rate of blood transfusion per year during the same time period, however, remained constant at 22%.

In another study published online November 9, researchers found that overall survival may be a reasonable primary endpoint when the median survival postprogession is less than 6 months, but it is too high a hurdle when it is longer than 12 months.

This study was undertaken to examine whether progression-free survival (PFS) or OS is the most appropriate endpoint in clinical trials of metastatic cancer, and to determine if it is reasonable to expect that treatment benefit in PFS carries over to OS.

To address these questions, Donald A. Berry, of the Department of Biostatistics, University of Texas M. D. Anderson Cancer Center in Houston, and colleagues simulated clinical trials with two arms having respective medians for PFS of 6 and 9 months. Researchers partitioned OS into two parts and expressed it as the sum of PFS and SPP. Probabilities of a benefit in OS were determined for various median SPP, by assuming no treatment-related difference in SPP, and for different P values for PFS.

They found that, at a P value for improved PFS of .001, there was a greater than 90% probability for statistical significance in OS if the median SPP was 2 months. However, the probability for statistical significance was less than 20% if the median SPP was 24 months.

Unexpectedly, inflammation markers do not appear to be involved with the chemopreventative effect of aspirin on colorectal adenomas, according to a brief communication published online October 12.

Aspirin has been shown to prevent the recurrence of colorectal polyps, but it's not clear how it works. One hypothesis is that it may affect the levels of substances, such as C-reactive protein and others, that are markers of inflammation.

To study this, Gloria Y.F.Ho., of the department of Epidemiology & Population Health, at Albert Einstein College of Medicine in Bronx, N.Y., and colleagues examined changes in plasma levels of five inflammation markers—C-reactive protein, interleukin 6, tumor necrosis factor, soluble TNF receptor type II, and IL-1 receptor antagonist—at baseline and at year 3 of 884 subjects. The trial had three aspirin groups (including an aspirin placebo group) and two folic acid groups (including a folate placebo group).

Changes in levels of all five inflammation markers were not associated with adenoma recurrence. For those who did not receive folic acid, C-reactive protein levels in those in the 325 mg/d aspirin group changed very little, whereas it was statistically significantly increased in the placebo group. For subjects who received folic acid, the reverse association was observed.

That’s it for this edition of the JNCI podcast.

As always, find these studies online at jnci.oxfordjournals.org . Also check out this month’s JNCI interview with Dr. Lisa Schwartz and Steve Woloshin, two of the authors from this issue’s editorial on news media and cancer research.